Comparative receptor based brain delivery of tramadol-loaded poly(lactic-co-glycolic acid) nanoparticles.

Receptor mediated endocytosis or transcytosis has been reported for drug delivery across Blood-brain barrier (BBB) and hence, the aim of the present investigations was to prepare and compare brain targeting efficiency of tramadol-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles surface modified with transferrin (Tf) and lactoferrin (Lf). Nanoparticles of tramadol were prepared using nanoprecipitation technique and surface conjugated with Tf and Lf using epoxy linker. Prepared nanoparticles were characterized for their size, surface charge, drug entrapment, transmission electron microscopy and in vitro drug release. The surface density of Tf and Lf was estimated by protein estimation. The drug distribution in blood, brain and other tissues was studied in mice after intravenous administration. Tf and Lf anchored nanoparticles exhibit enhanced uptake with 2.38 and 3.85 folds higher targeting respectively in the brain when compared with unconjugated nanoparticles. The brain targeting observed for Lf anchored PLGA nanoparticles (Lf-TMD-PLGA-NP) was 1.62 folds that of Tf anchored PLGA nanoparticles (Tf-TMD-PLGA-NP). Hence, the study revealed Tf and specially Lf as promising ligand for enhanced brain deposition of tramadol.

Development and evaluation of a time-specific pulsatile-release tablet of aceclofenac: a solution for morning pain in rheumatoid arthritis.

The objective of this study was to develop and evaluate an oral chronomodulated drug delivery system (CDDS) for the treatment of rheumatoid arthritis with a distinct predetermined lag time of 6 h (+/- 0.25 h). The basic design of the system consisted of an inner core, an intermediate swelling layer and an external acid-resistant enteric layer applied by pan coating. Croscarmellose sodium was used as a disintegrant and swelling agent to create the desired rupturing pressure. A mixture of hydroxypropyl cellulose M (175 mg) and ethyl cellulose (25 mg) was used as an intermediate swelling layer. The lag time for the system was found to be independent of the effect of various parameters such as compression load, paddle rotation speed and pH of dissolution medium. For the enteric coating of the press-coated tablet an aqueous dispersion of Eudragit L30 D55 containing 15% of total solid content plasticized with 20 triethyl citrate was applied by conventional pan coater. An in vitro dissolution study of the prepared tablet was conducted initially for 2 h in simulated gastric fluid, and after that medium was changed to simulated intestinal fluid pH 6.8. A pharmacokinetic study was also used to establish in vitro methodology capable of predicting the subsequent in vivo performance of the time-dependent pulsatile-release system. Various pharmacokinetic parameters studied in rabbits as the animal model demonstrated that drug absorption was not influenced by the in vivo behavior of the pulsatile system. As per guidelines provided by the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use and the World Health Organization, the formulation was found to be stable.

Novel 99mTc radiolabeled quinazolinone derivative [Qn-In]: synthesis, evaluation and biodistribution studies in mice and rabbit.

A quinazolinone derivative as a novel non-peptidic CCK-B receptor antagonist designated as Qn-In, was synthesized, characterized by spectroscopic techniques and evaluated for radiopharmaceutical potential. The efficiency of labeling with (99m)Tc was greater than 98% and the complex was stable for about 7 hours at 37 degrees C in presence of serum. Affinity of Qn-In was determined to be in nanomolar range by competitive binding studies on cancer cell line MDA-MB-468. Bio-distribution of (99m)Tc labeled Qn-In in mice was examined by intravenous administration and time-activity curves were generated. The ligand showed binding to most of the organs, known to express CCK-B receptor. The lack of uptake in brain may be due to the inability of the complex to cross the blood-brain barrier. Our results show that (99m)Tc labeled Qn-In ligand provides a new template for further development of non-peptidic ligands for diagnosis and therapy of diseases related with CCK-B receptor.